Circulating Tumor DNA as a Prognostic Determinant in Small Cell Lung Cancer Patients Receiving Atezolizumab.
NOTCH
RB1
SCLC
TP53
atezolizumab
ctDNA
mutation
Journal
Journal of clinical medicine
ISSN: 2077-0383
Titre abrégé: J Clin Med
Pays: Switzerland
ID NLM: 101606588
Informations de publication
Date de publication:
27 Nov 2020
27 Nov 2020
Historique:
received:
22
10
2020
revised:
16
11
2020
accepted:
25
11
2020
entrez:
2
12
2020
pubmed:
3
12
2020
medline:
3
12
2020
Statut:
epublish
Résumé
The IFCT-1603 trial evaluated atezolizumab in small cell lung cancer (SCLC). The purpose of the present study was to determine whether circulating tumor DNA (ctDNA), prospectively collected at treatment initiation, was associated with the prognosis of SCLC, and whether it identified patients who benefited from atezolizumab. 68 patients were included in this study: 46 patients were treated with atezolizumab and 22 with conventional chemotherapy. Circulating DNA was extracted from plasma and NGS (Next Generation Sequencing) looked for mutations in the We found that 49/68 patients (70.6%) had detectable baseline ctDNA. The most frequently identified mutations were TP53 (32/49; 65.3%) and RB1 (25/49; 51.0%). Patients with detectable ctDNA had a significantly lower disease control rate at week 6 compared with patients with no detectable ctDNA, regardless of the nature of the treatment. Detection of ctDNA was associated with a poor OS prognosis. The detection of ctDNA at a relative abundance greater than the median value was significantly associated with poor overall survival (OS) and progression free survival (PFS). Interestingly, the benefit in overall survival (OS) associated with low ctDNA was more pronounced in patients treated with atezolizumab than in patients receiving chemotherapy. Among patients whose relative ctDNA abundance was below the median, those treated with atezolizumab tended to have higher OS than those in the chemotherapy arm. ctDNA is strongly associated with the prognosis of SCLC patients treated with second-line immunotherapy. Its analysis seems justified for future SCLC clinical trials.
Sections du résumé
BACKGROUND
BACKGROUND
The IFCT-1603 trial evaluated atezolizumab in small cell lung cancer (SCLC). The purpose of the present study was to determine whether circulating tumor DNA (ctDNA), prospectively collected at treatment initiation, was associated with the prognosis of SCLC, and whether it identified patients who benefited from atezolizumab.
METHODS
METHODS
68 patients were included in this study: 46 patients were treated with atezolizumab and 22 with conventional chemotherapy. Circulating DNA was extracted from plasma and NGS (Next Generation Sequencing) looked for mutations in the
RESULTS
RESULTS
We found that 49/68 patients (70.6%) had detectable baseline ctDNA. The most frequently identified mutations were TP53 (32/49; 65.3%) and RB1 (25/49; 51.0%). Patients with detectable ctDNA had a significantly lower disease control rate at week 6 compared with patients with no detectable ctDNA, regardless of the nature of the treatment. Detection of ctDNA was associated with a poor OS prognosis. The detection of ctDNA at a relative abundance greater than the median value was significantly associated with poor overall survival (OS) and progression free survival (PFS). Interestingly, the benefit in overall survival (OS) associated with low ctDNA was more pronounced in patients treated with atezolizumab than in patients receiving chemotherapy. Among patients whose relative ctDNA abundance was below the median, those treated with atezolizumab tended to have higher OS than those in the chemotherapy arm.
CONCLUSION
CONCLUSIONS
ctDNA is strongly associated with the prognosis of SCLC patients treated with second-line immunotherapy. Its analysis seems justified for future SCLC clinical trials.
Identifiants
pubmed: 33261056
pii: jcm9123861
doi: 10.3390/jcm9123861
pmc: PMC7760916
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Roche
ID : -
Organisme : IFCT
ID : -
Références
Clin Cancer Res. 2009 Jan 1;15(1):274-83
pubmed: 19118055
J Clin Oncol. 2007 May 20;25(15):2086-92
pubmed: 17513814
J Thorac Dis. 2019 Jan;11(Suppl 1):S102-S112
pubmed: 30775033
J Cancer. 2020 Feb 3;11(8):2113-2122
pubmed: 32127938
Cancers (Basel). 2020 Jul 11;12(7):
pubmed: 32664549
Lung Cancer. 2017 Feb;104:16-23
pubmed: 28212995
J Clin Oncol. 2015 Dec 1;33(34):4106-11
pubmed: 26351333
J Thorac Oncol. 2013 May;8(5):587-98
pubmed: 23546044
Clin Chem. 2016 Nov;62(11):1492-1503
pubmed: 27624137
J Clin Oncol. 2013 Sep 10;31(26):3205-11
pubmed: 23918947
J Thorac Dis. 2019 Jan;11(Suppl 1):S113-S126
pubmed: 30775034
Lung Cancer. 2017 Oct;112:118-125
pubmed: 29191584
N Engl J Med. 2018 Dec 6;379(23):2220-2229
pubmed: 30280641
BMC Cancer. 2018 Jul 9;18(1):726
pubmed: 29986670
J Thorac Oncol. 2020 Feb;15(2):216-230
pubmed: 31629061
Nat Commun. 2018 Aug 6;9(1):3114
pubmed: 30082701
Oncotarget. 2017 May 16;8(20):33922-33932
pubmed: 28430611
J Cancer. 2016 Jun 04;7(9):1105-13
pubmed: 27326254
J Clin Oncol. 2020 Jul 20;38(21):2369-2379
pubmed: 32468956
J Thorac Oncol. 2018 Jan;13(1):112-123
pubmed: 28951314
Lancet. 2019 Nov 23;394(10212):1929-1939
pubmed: 31590988
Ann Oncol. 2012 Nov;23(11):2937-2942
pubmed: 22689177
Nature. 2015 Aug 6;524(7563):47-53
pubmed: 26168399
J Thorac Oncol. 2019 May;14(5):903-913
pubmed: 30664989
J Clin Oncol. 2012 Feb 10;30(5):525-32
pubmed: 22253462
J Thorac Oncol. 2012 Mar;7(3):512-9
pubmed: 22258473